pavel babal - Academia.edu (original) (raw)
Papers by pavel babal
Frontiers in nuclear medicine, Feb 16, 2022
Biologia (Bratislava), 2000
Journal of Clinical Oncology, May 20, 2012
e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer.... more e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. PARP inhibitors represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate poly(ADP-ribose)polymerase-1 (PARP1) expression in TGCTs and to correlate expression patterns with clinico-pathological variables. Methods: In this translational study, tumor specimens from 124 patients with GCTs were identified. PARP1 expression was detected by immunohistochemistry using monoclonal antibody, scored by the multiplicative quickscore (QS) method and compared to PARP1 expression in testicular tissue of normal testis. The QS was calculated by multiplying the percentage score by the staining intensity score to yield a minimum value of 0 and a maximum value of 18. Based on the QS nuclear PARP1 expression was graded as low (0–9) or high (10–18). Results: We observed higher expression of PARP1 in testicular tumors compared to normal tissue of testis (mean QS = 10.04 vs. 3.60, p < 0.0000001). Mean QS ± SD for each histological subtype was following: intratubular germ cell neoplasia (ITGCN) = 18.00 ± 0.00, embryonal carcinoma = 9.62 ± 5.64, seminoma = 9.74 ± 6.51, yolc sac tumor = 7.8 ± 7.20, teratoma = 5.87 ± 5.34, and choriocarcinoma = 4.50 ± 8.33. The PARP1 overexpression (QS > 9) was most often detected in ITGCN (100% of specimen with PARP1 overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolc sac tumor (33.3%), teratoma (26.7%), and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimen. There was no association between PARP1 expression and clinical variables. Conclusions: PARP1 overexpression is an early event in the development of TGCTs. We suggest that PARP1 could represent a novel treatment target in TGCTs and the assessment of PARP1 expression in tumor samples may lead to the consideration of TGCTs patients for PARP inhibitor therapy.
PubMed, 2008
Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3%... more Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3% of all leukemias in adults. The skin lesions were described in about 10-12% of patients. Vasculitis in lymphoproliferative disease is relatively uncommon and may predate the diagnosis of lymphoproliferative disease. A 54-year old female with one month history of general symptoms and sudden onset of maculopapular exanthema on the skin, suffered from anemia, leukopenia and thrombocytopenia. Examination of the skin biopsy revealed lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44 antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow and of the peripheral blood cells that revealed pathological cell population with expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with a single dose of cladribrine. The patient with acute vasculitis should be screened and monitored for possible lymphoproliferative diseases. Skin manifestation of acute vasculitis accompanied with hairy cells may be the first manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the first line of therapy for HCL and induces a total response in more than 80% of cases with HCL.
Springer eBooks, 1991
The putative role of viruses, especially of herpes simplex virus (HSV), in the etiology of schizo... more The putative role of viruses, especially of herpes simplex virus (HSV), in the etiology of schizophrenia and related mental disorders has been discussed since the finding of elevated antibody levels to HSV type 1 in psychiatric patients (Rimon and Halonen, 1969). Libikova (1983) found that the geometric mean titer of neutralizing antibodies (NA) to HSV type 1 was higher in each age group of schizophrenic (SCH) patients as compared to controls. The hemagglutination inhibition antibodies to measles virus and the complement fixation antibodies to varicella—zoster virus were not increased when tested in the same sera. Repeated serologic investigation with a great number of sera from SCH patients and controls confirmed the elevated NA titers in the presence and absence of complement in the sera of domestic SCH patients but not in those obtained from abroad (Rajcani et al., 1987). Using ELISA and a sensitive neutralization test in the presence of complement, we found that both tests were positive in 42 of 262 (16%) CSF samples from SCH patients. The NA titered ≥ 4 and the ELISA ≥ 128 (Bartova et al., 1987). For this reason we decided to compare the results of both tests in a further representative group of SCH patients.
Biochemical Journal, Apr 15, 1994
International Journal of Radiation Biology, Aug 17, 2022
Acta Ophthalmologica, 2022
The FASEB Journal, May 1, 2022
PubMed, Nov 20, 2016
Aim: The aim is to assess the BRAF gene mutations in patients with posterior uveal melanoma. Mate... more Aim: The aim is to assess the BRAF gene mutations in patients with posterior uveal melanoma. Material and methods: Retrospective analysis of the group of patients with malignant melanoma of the uvea, who were indicated to enucleation between 1.1 2015 to 1.3.2016. We analyzed stage of uveal melanoma, volume, cell type and BRAF gene mutations. Results: In clinical study of 20 patients after enucleation due to uveal melanoma at the Department of Ophthalmology in Bratislava, patient age was ranged from 22 to 89 years with a median of 62 years. In 14 patients (70 %) enucleation was the primary treatment and in 6 patients (30 %) enucleation was after irradiation (brachytherapy, Leksell gama knife, linear accelerator). In 17 cases (85 %) the mutation of the BRAF gene was negative and in 3 cases the sample was not assessable for the BRAF mutation. Conclusion: BRAF gene mutation is confirmed by several studies found in malignant melanoma of the skin. The histopathology findings in our group did not confirmed our theory, that since the uveal melanoma itself has the similar origin as skin melanoma, should also contain a BRAF mutation.Key words: malignant melanoma of the uvea, mutation of the BRAF gene, chromosomal abnormalities as a prognostic factor.
PubMed, Jan 20, 2016
Aim: Non-melanoma skin cancer cases in the European population are increasing. Basal cell carcino... more Aim: Non-melanoma skin cancer cases in the European population are increasing. Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer of the eyelids and in the inner corner of the eyelid. Due to the latest statistics compiled and published in 2008 in the Slovak Republic (SR) there were registered 5,173 cases of non-melanoma skin cancer (C44 according to ICD-10) in both sexes together (of which women accounted for 51.2 %). The proportion of non-melanoma skin cancer accounted for 17.2 % (16.3 % of men and 18 % of women) of the total number of all reported cancer cases (n = 30,144). The aim of this study is to evaluate the number of clinical relapses in a group of patients. Material: Retrospectively analyzed data from the medical records of patients with newly detected basal cell carcinoma in period between Jan. 1 2008 to Dec. 31 2013 who underwent surgery and outpatient follow-up at the Department of Ophthalmology and the University Hospital in Bratislava. Methods: The incidence of relapse was evaluated up to date Dec. 31 2014. We followed the following parameters: location and tumor size, TNM classification, histopathological degree of differentiation, the edges of excised tissue and evaluated recurrence rate separately for each parameter. Statistics were analyzed by chi2 test, which was found to be significant for P < 0.05. The results of continuous parameters were expressed as arithmetic mean ± standard deviation. Results: At the Department of Ophthalmology Faculty of Medicine and UNB, Ruzinov Hospital, in Bratislava, in the period 2008 - 2013 were treated 219 basal cell carcinomas in 217 patients and basal cell carcinoma was histologically confirmed. Basal cell carcinomas were divided into groups according to the stage: G1 (n = 139), G 1-2 (n = 41) and G 2 (n = 39). Localization was more frequent on left side (n = 112) compared to the right one (n = 107). We recorded significantly lower incidence (n = 5) in the area - angulus externus, prevalent occurrence was in the inner area - angulus internus (n = 65). The incidence in the lower eyelid (palpebra inferior) was recorded more frequently (n = 127) as in the upper eyelid (palpebra superior) - (n = 24). During these six years period we have seen 11 recurrences (5.02 %). Exenteration of the orbit was indicated in 5 cases (2.7 %). Conclusion: When monitoring patients with newly detected eyelid basal cell carcinoma, operated at the Department of Ophthalmology Faculty of Medicine and UNB in period 2008-2013, incidence of recurrence was recorded in 11 cases, accounting for 5.02 %, which is about one percentage point lower share than in the previous reporting period from period 2005 -2007 from the same Department. The occurrence of relapses corresponds to those in the literature. None of the clinical parameters statistically did affect significantly the incidence of relapses. Key words: eyelid basal cell carcinoma, non-melanoma skin cancer, tumors eyelashes.
The Open Neurology Journal, Oct 3, 2022
Objective: After the outbreak of the global pandemic caused by SARS-CoV-2 infection at the end of... more Objective: After the outbreak of the global pandemic caused by SARS-CoV-2 infection at the end of the year 2019, it took one year to start vaccination against this infection with products from various manufacturers. As of November 2021, more than 8 billion vaccine doses against COVID-19 have been administered, which is essentially linked to a spike in adverse events reports following these vaccinations, including a number of neurological adverse events.
Clinical and translational medicine, Jul 1, 2023
Research Square (Research Square), Jan 25, 2023
Background: Despite outstanding advances in understanding the genetic background of uveal melanom... more Background: Despite outstanding advances in understanding the genetic background of uveal melanoma (UM) development and prognosis, the role of DNA methylation reprogramming remains elusive. This study aims to clarify the extent of DNA methylation deregulation in the context of gene expression changes and its utility as a reliable prognostic biomarker. Methods: Transcriptomic and DNA methylation landscapes in 25 high-and low-risk UMs were interrogated by Agilent SurePrint G3 Human Gene Expression 8×60K v2 Microarray and Human In nium Methylation EPIC Bead Chip array, respectively. DNA methylation and gene expression of the nine top discriminatory genes, selected by the integrative analysis, were validated by pyrosequencing and qPCR in 58 tissues. Results: Among 2,262 differentially expressed genes discovered in UM samples differing in metastatic risk, 60 were epigenetic regulators, mostly histone modi ers and chromatin remodelers. A total of 44,398 CpGs were differentially methylated, 27,810 hypomethylated, and 16,588 hypermethylated in high-risk tumors, with Δβ values ranging between-0.78 and 0.79. By integrative analysis, 944 differentially expressed DNA methylation-regulated genes were revealed, 635 hypomethylated/upregulated, and 309 hypermethylated/downregulated. Aberrant DNA methylation in high-risk tumors was associated with the deregulation of key oncogenic pathways such as EGFR tyrosine kinase inhibitor resistance, focal adhesion, proteoglycans in cancer, PI3K-Akt signaling, or ECM-receptor interaction. Notably, the DNA methylation values of nine genes, HTR2B, AHNAK2, CALHM2, SLC25A38, EDNRB, TLR1, RNF43, IL12RB2, and MEGF10, validated by pyrosequencing, demonstrated excellent risk group prediction accuracies (AUCs ranging between 0.870 and 0.956). Moreover, CALHM2 hypomethylation and MEGF10, TLR1 hypermethylation, as well as two three-gene methylation signatures, Signature 1 combining AHNAK2, CALHM2, and IL12RB and Signature 2 AHNAK2, CALHM2, and SLC25A38 genes, correlated with shorter overall survival (
Case Reports in Ophthalmology, Apr 5, 2022
The report aims to present the case of intraocular leiomyoma. We conducted a case study on a pati... more The report aims to present the case of intraocular leiomyoma. We conducted a case study on a patient who presented with an intraocular tumour. After examination, including magnetic resonance, positron emission tomography with computed tomography, B-scan, we performed surgery-enucleation of the eye globe with histological verification of tumour mass. Histological analysis of enucleated eyes proved intraocular leiomyoma. Leiomyoma is a rare intraocular tumour, which is clinically challenging to recognize; therefore, histological confirmation is most often required.
Frontiers in nuclear medicine, Feb 16, 2022
Biologia (Bratislava), 2000
Journal of Clinical Oncology, May 20, 2012
e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer.... more e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. PARP inhibitors represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate poly(ADP-ribose)polymerase-1 (PARP1) expression in TGCTs and to correlate expression patterns with clinico-pathological variables. Methods: In this translational study, tumor specimens from 124 patients with GCTs were identified. PARP1 expression was detected by immunohistochemistry using monoclonal antibody, scored by the multiplicative quickscore (QS) method and compared to PARP1 expression in testicular tissue of normal testis. The QS was calculated by multiplying the percentage score by the staining intensity score to yield a minimum value of 0 and a maximum value of 18. Based on the QS nuclear PARP1 expression was graded as low (0–9) or high (10–18). Results: We observed higher expression of PARP1 in testicular tumors compared to normal tissue of testis (mean QS = 10.04 vs. 3.60, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0000001). Mean QS ± SD for each histological subtype was following: intratubular germ cell neoplasia (ITGCN) = 18.00 ± 0.00, embryonal carcinoma = 9.62 ± 5.64, seminoma = 9.74 ± 6.51, yolc sac tumor = 7.8 ± 7.20, teratoma = 5.87 ± 5.34, and choriocarcinoma = 4.50 ± 8.33. The PARP1 overexpression (QS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 9) was most often detected in ITGCN (100% of specimen with PARP1 overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolc sac tumor (33.3%), teratoma (26.7%), and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimen. There was no association between PARP1 expression and clinical variables. Conclusions: PARP1 overexpression is an early event in the development of TGCTs. We suggest that PARP1 could represent a novel treatment target in TGCTs and the assessment of PARP1 expression in tumor samples may lead to the consideration of TGCTs patients for PARP inhibitor therapy.
PubMed, 2008
Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3%... more Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3% of all leukemias in adults. The skin lesions were described in about 10-12% of patients. Vasculitis in lymphoproliferative disease is relatively uncommon and may predate the diagnosis of lymphoproliferative disease. A 54-year old female with one month history of general symptoms and sudden onset of maculopapular exanthema on the skin, suffered from anemia, leukopenia and thrombocytopenia. Examination of the skin biopsy revealed lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44 antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow and of the peripheral blood cells that revealed pathological cell population with expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with a single dose of cladribrine. The patient with acute vasculitis should be screened and monitored for possible lymphoproliferative diseases. Skin manifestation of acute vasculitis accompanied with hairy cells may be the first manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the first line of therapy for HCL and induces a total response in more than 80% of cases with HCL.
Springer eBooks, 1991
The putative role of viruses, especially of herpes simplex virus (HSV), in the etiology of schizo... more The putative role of viruses, especially of herpes simplex virus (HSV), in the etiology of schizophrenia and related mental disorders has been discussed since the finding of elevated antibody levels to HSV type 1 in psychiatric patients (Rimon and Halonen, 1969). Libikova (1983) found that the geometric mean titer of neutralizing antibodies (NA) to HSV type 1 was higher in each age group of schizophrenic (SCH) patients as compared to controls. The hemagglutination inhibition antibodies to measles virus and the complement fixation antibodies to varicella—zoster virus were not increased when tested in the same sera. Repeated serologic investigation with a great number of sera from SCH patients and controls confirmed the elevated NA titers in the presence and absence of complement in the sera of domestic SCH patients but not in those obtained from abroad (Rajcani et al., 1987). Using ELISA and a sensitive neutralization test in the presence of complement, we found that both tests were positive in 42 of 262 (16%) CSF samples from SCH patients. The NA titered ≥ 4 and the ELISA ≥ 128 (Bartova et al., 1987). For this reason we decided to compare the results of both tests in a further representative group of SCH patients.
Biochemical Journal, Apr 15, 1994
International Journal of Radiation Biology, Aug 17, 2022
Acta Ophthalmologica, 2022
The FASEB Journal, May 1, 2022
PubMed, Nov 20, 2016
Aim: The aim is to assess the BRAF gene mutations in patients with posterior uveal melanoma. Mate... more Aim: The aim is to assess the BRAF gene mutations in patients with posterior uveal melanoma. Material and methods: Retrospective analysis of the group of patients with malignant melanoma of the uvea, who were indicated to enucleation between 1.1 2015 to 1.3.2016. We analyzed stage of uveal melanoma, volume, cell type and BRAF gene mutations. Results: In clinical study of 20 patients after enucleation due to uveal melanoma at the Department of Ophthalmology in Bratislava, patient age was ranged from 22 to 89 years with a median of 62 years. In 14 patients (70 %) enucleation was the primary treatment and in 6 patients (30 %) enucleation was after irradiation (brachytherapy, Leksell gama knife, linear accelerator). In 17 cases (85 %) the mutation of the BRAF gene was negative and in 3 cases the sample was not assessable for the BRAF mutation. Conclusion: BRAF gene mutation is confirmed by several studies found in malignant melanoma of the skin. The histopathology findings in our group did not confirmed our theory, that since the uveal melanoma itself has the similar origin as skin melanoma, should also contain a BRAF mutation.Key words: malignant melanoma of the uvea, mutation of the BRAF gene, chromosomal abnormalities as a prognostic factor.
PubMed, Jan 20, 2016
Aim: Non-melanoma skin cancer cases in the European population are increasing. Basal cell carcino... more Aim: Non-melanoma skin cancer cases in the European population are increasing. Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer of the eyelids and in the inner corner of the eyelid. Due to the latest statistics compiled and published in 2008 in the Slovak Republic (SR) there were registered 5,173 cases of non-melanoma skin cancer (C44 according to ICD-10) in both sexes together (of which women accounted for 51.2 %). The proportion of non-melanoma skin cancer accounted for 17.2 % (16.3 % of men and 18 % of women) of the total number of all reported cancer cases (n = 30,144). The aim of this study is to evaluate the number of clinical relapses in a group of patients. Material: Retrospectively analyzed data from the medical records of patients with newly detected basal cell carcinoma in period between Jan. 1 2008 to Dec. 31 2013 who underwent surgery and outpatient follow-up at the Department of Ophthalmology and the University Hospital in Bratislava. Methods: The incidence of relapse was evaluated up to date Dec. 31 2014. We followed the following parameters: location and tumor size, TNM classification, histopathological degree of differentiation, the edges of excised tissue and evaluated recurrence rate separately for each parameter. Statistics were analyzed by chi2 test, which was found to be significant for P < 0.05. The results of continuous parameters were expressed as arithmetic mean ± standard deviation. Results: At the Department of Ophthalmology Faculty of Medicine and UNB, Ruzinov Hospital, in Bratislava, in the period 2008 - 2013 were treated 219 basal cell carcinomas in 217 patients and basal cell carcinoma was histologically confirmed. Basal cell carcinomas were divided into groups according to the stage: G1 (n = 139), G 1-2 (n = 41) and G 2 (n = 39). Localization was more frequent on left side (n = 112) compared to the right one (n = 107). We recorded significantly lower incidence (n = 5) in the area - angulus externus, prevalent occurrence was in the inner area - angulus internus (n = 65). The incidence in the lower eyelid (palpebra inferior) was recorded more frequently (n = 127) as in the upper eyelid (palpebra superior) - (n = 24). During these six years period we have seen 11 recurrences (5.02 %). Exenteration of the orbit was indicated in 5 cases (2.7 %). Conclusion: When monitoring patients with newly detected eyelid basal cell carcinoma, operated at the Department of Ophthalmology Faculty of Medicine and UNB in period 2008-2013, incidence of recurrence was recorded in 11 cases, accounting for 5.02 %, which is about one percentage point lower share than in the previous reporting period from period 2005 -2007 from the same Department. The occurrence of relapses corresponds to those in the literature. None of the clinical parameters statistically did affect significantly the incidence of relapses. Key words: eyelid basal cell carcinoma, non-melanoma skin cancer, tumors eyelashes.
The Open Neurology Journal, Oct 3, 2022
Objective: After the outbreak of the global pandemic caused by SARS-CoV-2 infection at the end of... more Objective: After the outbreak of the global pandemic caused by SARS-CoV-2 infection at the end of the year 2019, it took one year to start vaccination against this infection with products from various manufacturers. As of November 2021, more than 8 billion vaccine doses against COVID-19 have been administered, which is essentially linked to a spike in adverse events reports following these vaccinations, including a number of neurological adverse events.
Clinical and translational medicine, Jul 1, 2023
Research Square (Research Square), Jan 25, 2023
Background: Despite outstanding advances in understanding the genetic background of uveal melanom... more Background: Despite outstanding advances in understanding the genetic background of uveal melanoma (UM) development and prognosis, the role of DNA methylation reprogramming remains elusive. This study aims to clarify the extent of DNA methylation deregulation in the context of gene expression changes and its utility as a reliable prognostic biomarker. Methods: Transcriptomic and DNA methylation landscapes in 25 high-and low-risk UMs were interrogated by Agilent SurePrint G3 Human Gene Expression 8×60K v2 Microarray and Human In nium Methylation EPIC Bead Chip array, respectively. DNA methylation and gene expression of the nine top discriminatory genes, selected by the integrative analysis, were validated by pyrosequencing and qPCR in 58 tissues. Results: Among 2,262 differentially expressed genes discovered in UM samples differing in metastatic risk, 60 were epigenetic regulators, mostly histone modi ers and chromatin remodelers. A total of 44,398 CpGs were differentially methylated, 27,810 hypomethylated, and 16,588 hypermethylated in high-risk tumors, with Δβ values ranging between-0.78 and 0.79. By integrative analysis, 944 differentially expressed DNA methylation-regulated genes were revealed, 635 hypomethylated/upregulated, and 309 hypermethylated/downregulated. Aberrant DNA methylation in high-risk tumors was associated with the deregulation of key oncogenic pathways such as EGFR tyrosine kinase inhibitor resistance, focal adhesion, proteoglycans in cancer, PI3K-Akt signaling, or ECM-receptor interaction. Notably, the DNA methylation values of nine genes, HTR2B, AHNAK2, CALHM2, SLC25A38, EDNRB, TLR1, RNF43, IL12RB2, and MEGF10, validated by pyrosequencing, demonstrated excellent risk group prediction accuracies (AUCs ranging between 0.870 and 0.956). Moreover, CALHM2 hypomethylation and MEGF10, TLR1 hypermethylation, as well as two three-gene methylation signatures, Signature 1 combining AHNAK2, CALHM2, and IL12RB and Signature 2 AHNAK2, CALHM2, and SLC25A38 genes, correlated with shorter overall survival (
Case Reports in Ophthalmology, Apr 5, 2022
The report aims to present the case of intraocular leiomyoma. We conducted a case study on a pati... more The report aims to present the case of intraocular leiomyoma. We conducted a case study on a patient who presented with an intraocular tumour. After examination, including magnetic resonance, positron emission tomography with computed tomography, B-scan, we performed surgery-enucleation of the eye globe with histological verification of tumour mass. Histological analysis of enucleated eyes proved intraocular leiomyoma. Leiomyoma is a rare intraocular tumour, which is clinically challenging to recognize; therefore, histological confirmation is most often required.